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Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts

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Abstract

Background

Neuronal signaling has been implicated in the pathophysiology of multiple malignancies. In biliary tract cancers (BTCs), tumor cell expression of nerve growth factor (NGF) and its receptor neurotrophic tropomyosin receptor kinase (NTRK) has been reported in Asian patients and linked to inferior clinical outcome. Furthermore, NTRK fusions have emerged as a promising target in various cancers. Expression patterns of these markers in Caucasian patients remain unknown.

Methods

In this study, 106 patients with BTCs were included. Immunohistochemistry for pan-NTRK and NGF-beta was performed on > 90 samples of this cohort. Additionally, samples from two independent cohorts, incorporating 254 cases, were used to confirm the findings of the original cohort.

Results

While expression of pan-NTRK and NGF-beta was readily detectable in peri-tumoral nerves, these markers were not detectable in malignant epithelial cells in our cohort.

Conclusions

In a large cohort of Caucasian patients with BTC, NTRK and NGF-beta were not detectable, underscoring potential differences between Caucasian and Asian patient populations.

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Abbreviations

BTC:

Biliary tract cancer

ECC:

Extrahepatic cholangiocarcinoma

FFPE:

Formalin-fixed, paraffin-embedded

ICC:

Intrahepatic cholangiocarcinoma

NGF:

Nerve growth factor

NTRK:

Neurotrophic tropomyosin receptor kinase

TMA:

Tissue microarray

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Authors and Affiliations

  1. Department of Medicine III, University Hospital, Ludwig Maximilian University, 81377, Munich, Germany

    C. B. Westphalen, A. Preinfalk, S. Kruger, M. Haas, V. Heinemann, M. von Bergwelt-Baildon & S. Boeck

  2. Comprehensive Cancer Center Munich, 80336, Munich, Germany

    C. B. Westphalen, V. Heinemann, M. von Bergwelt-Baildon & S. Boeck

  3. Department of Surgery, University Hospital, Ludwig Maximilian University, 81377, Munich, Germany

    B. W. Renz & J. Werner

  4. OptiPath, Pathology Joint Practice, 60487, Frankfurt, Germany

    M.-O. Riener

  5. Institute of Pathology, University Hospital Erlangen-Nuremberg, 91054, Erlangen, Germany

    M.-O. Riener

  6. Department of Pathology and Molecular Pathology, University Hospital Zürich, 8091, Zurich, Switzerland

    A. Weber

  7. Institute of Pathology, Faculty of Medicine, Ludwig Maximilian University, 80337, Munich, Germany

    T. Kirchner & S. Ormanns

  8. Institute of Pathology, University Hospital Essen, 45147, Essen, Germany

    H. A. Baba

  9. Division of Solid Tumor Translational Oncology (DKTK, Partner Site Essen), West German Cancer Center, University Hospital Essen, 45147, Essen, Germany

    J. T. Siveke

  10. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany

    J. T. Siveke

Authors
  1. C. B. Westphalen
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  2. A. Preinfalk
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  3. S. Kruger
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  4. M. Haas
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  8. T. Kirchner
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  9. J. Werner
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  13. J. T. Siveke
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  14. S. Ormanns
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  15. S. Boeck
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Contributions

CBW: Design of the study, data analysis, writing of the manuscript; provided funding; AP: study design, data collection, data analysis; SK: data collection, intellectual input, critical discussion of the manuscript, MH: data collection, manuscript writing; BWR: data collection, discussion of the manuscript, technical support; MOR: provided materials (TMA) and patient data, writing and discussion of the manuscript; AW: provided patient materials (TMA) and patient data; TK: provided patient materials for TMA construction, critical discussion of the manuscript; JW: provided patient data; VH: study design, manuscript writing; MvB: provided patient data, writing and discussion of the manuscript; HAB: provided patient materials (TMA) and patient data; discussion and writing of the manuscript; JTS: provided patient materials (TMA) and patient data; discussion and writing of the manuscript; SO: construction of TMA; TMA staining, data analysis; SB: study design, project management, writing and discussion of the manuscript.

Corresponding author

Correspondence to C. B. Westphalen.

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Conflict of interest

The authors declare no conflict of interest.

Ethics approval

This retrospective study was carried out according to the recommendations of local authorities, the local ethics committee of the Medical Faculty of the University of Munich (Approval Number 285-15) and of the Medical Faculty of the University Duisburg-Essen (Approval Number 13-5638-BO) and in accordance with the Declaration of Helsinki.

Informed consent

For this study, participants provided informed consent when necessary.

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Westphalen, C.B., Preinfalk, A., Kruger, S. et al. Neurotrophic tropomyosin receptor kinase (NTRK) and nerve growth factor (NGF) are not expressed in Caucasian patients with biliary tract cancers: pooled data from three independent cohorts. Clin Transl Oncol 21, 1108–1111 (2019). https://doi.org/10.1007/s12094-018-02030-6

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  • DOI: https://doi.org/10.1007/s12094-018-02030-6

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